Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro.

Area of Science:

• Developmental Biology
• Neuroscience
• Stem Cell Biology

Background:

• Peripheral nervous system (PNS) development involves complex interactions between neural crest cells (NCCs) and their microenvironment.
• Understanding human NCC induction, migration, and differentiation is crucial for regenerative medicine and disease modeling.

Purpose of the Study:

• To develop a novel neuro-mesodermal assembloid model recapitulating key aspects of human PNS development.
• To investigate the intricate crosstalk between developing neuroectoderm, mesoderm, and vascular components.

Main Methods:

• Generation of a neuro-mesodermal assembloid model from human cells.
• Analysis of neural crest cell (NCC) induction, migration, and differentiation into sensory and sympathetic ganglia.
• Assessment of neurovascular interactions and functional maturation of sensory neurons.

Main Results:

• The assembloid model successfully recapitulated NCC induction, migration, and formation of sensory and sympathetic ganglia.
• Developing peripheral ganglia projected axons into both neural and mesodermal compartments, associating with Schwann cells.
• Functional analysis revealed sensory ganglia responded to capsaicin, and a neurovascular niche formed through interactions with a developing vascular plexus.

Conclusions:

• The novel neuro-mesodermal assembloid provides a powerful platform for studying human PNS development and neurocristopathies.
• This model facilitates investigation of neuro-mesodermal and neuro-vascular crosstalk, crucial for understanding tissue development and homeostasis.
• The model holds potential for drug screening and toxicity testing related to PNS development and function.